The objective of the proposed research is to study means of enhancing the radiation response of anoxic and hypoxic cells in vitro and in vivo. Cell culture systems including plateau phase and dense suspensions of animal and human tumor cells, multicell spheroids, and the EMT-6 solid tumor will be used. We will attempt to determine the degree to which the radiation response of cells may be improved by insulin, oxygen-mimicking drugs, respiratory inhibitors and glucose analogues. Our studies are also concerned with increasing the cytotoxicity of electron affinic drugs and glucose analogues toward hypoxic-anoxic cells. We plan to determine the cytotoxicity of electron affinic drugs in the presence of ascorbate; the drug-ascorbate reaction produces dehydroascorbate as well as reduced drug intermediates, all of which may be cytotoxic to hypoxic cells. The prior removal of hypoxic-anoxic cells or their improved oxygenation would enhance the radiation response of tumors to radiation. We anticipate that our findings will prove relevant to clinical radiotherapy.